Anatomical phenotyping and staging of brain tumours

Abstract

Abstract Unlike other tumors, the anatomical extent of brain tumors is not objectified and quantified through staging. Staging systems are based on understanding the anatomical sequence of tumor progression and its relationship to histopathological dedifferentiation and survival. The aim of this study was to describe the spatiotemporal phenotype of the most frequent brain tumor entities, to assess the association of anatomical tumor features with survival probability and to develop a staging system for WHO grade 2 and 3 gliomas and glioblastoma. Anatomical phenotyping was performed on a consecutive cohort of 1000 patients with first diagnosis of a primary or secondary brain tumor. Tumor probability in different topographic, phylogenetic and ontogenetic parcellation units was assessed on preoperative MRI through normalization of the relative tumor prevalence to the relative volume of the respective structure. We analyzed the spatiotemporal tumor dynamics by cross-referencing preoperative against preceding and subsequent MRIs of the respective patient. The association between anatomical phenotype and outcome defined prognostically critical anatomical tumor features at diagnosis. Based on a hypothesized sequence of anatomical tumor progression, we developed a three-level staging system for WHO grade 2 and 3 gliomas and glioblastoma. This staging system was validated internally in the original cohort and externally in an independent cohort of 300 consecutive patients. While primary central nervous system lymphoma showed highest probability along white matter tracts, metastases enriched along terminal arterial flow areas. Neuroepithelial tumors mapped along all sectors of the ventriculocortical axis, while adjacent units were spared, consistent with a transpallial behavior within phylo-ontogenetic radial units. Their topographic pattern correlated with morphogenetic processes of convergence and divergence of radial units during phylo- and ontogenesis. While a ventriculofugal growth dominated in neuroepithelial tumors, a gradual deviation from this neuroepithelial spatiotemporal behavior was found with progressive histopathological dedifferentiation. The proposed three-level staging system for WHO grade 2 and 3 gliomas and glioblastoma correlated with the degree of histological dedifferentiation and proved accurate in terms of survival upon both internal and external validation. In conclusion, this study identified specific spatiotemporal phenotypes in brain tumors through topographic probability and growth pattern assessment. The association of anatomical tumor features with survival defined critical steps in the anatomical sequence of neuroepithelial tumor progression, based on which a staging system for WHO grade 2 and 3 gliomas and glioblastoma was developed and validated.